Nested balloon cryotherapy

ABSTRACT

A cryotherapy system includes a cryotherapy catheter having an inflatable balloon portion and a pressure regulator. The inflatable balloon portion includes an outer balloon and an inner balloon within the outer balloon. The inner balloon is configured to receive during a cryotherapy procedure a cryogenic agent for extracting heat from body tissue at a desired location. The inflatable balloon portion is at a distal end of the cryotherapy catheter. The pressure regulator is adapted to maintain a positive pressure between the inner balloon and the outer balloon during a cryotherapy procedure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/300,220, filed Feb. 1, 2010, the entire disclosure of which isincorporated herein by reference.

BACKGROUND

Atrial fibrillation is a condition that results from abnormal electricalactivity within the heart. This abnormal electrical activity mayoriginate from various focal centers of the heart, and the electricalactivity generally decreases the efficiency with which the heart pumpsblood. It is believed that some of the focal centers reside in thepulmonary veins of the left atrium. It is further believed that atrialfibrillation can be reduced or controlled by structurally altering orablating the tissue at or near the focal centers of the abnormalelectrical activity to form a “conduction block.”

One method of structurally altering tissue of the heart and pulmonaryveins is to make, for example during open-heart surgery, a series ofincisions in a maze-like pattern in the atria, and sew the incisionsback together. As the incisions heal, scar tissue forms, and the scartissue may block the conductive pathways thought to cause atrialfibrillation. The procedure, which was developed under the direction ofDr. James Cox and refined over a period of years, may be referred to asa “maze” procedure, a “Cox maze” procedure, a “Cox maze III” procedure;or the procedure may be referred to by various other names.

A less invasive method of structurally altering heart tissue andpulmonary veins involves ablating tissue through the use of an ablationcatheter. One type of ablation catheter, for example, delivers radiofrequency (RF) energy to ablate tissue; another example ablationcatheter ablates tissue with a heat source; another example ablationcatheter delivers cryotherapy to ablate tissue by freezing it.

Cryotherapy may be delivered to an appropriate treatment site inside apatient's heart or circulatory system with a cryotherapy catheter. Acryotherapy catheter generally includes a treatment member at its distalend, such as an inflatable balloon having a cooling chamber inside. Todeliver the cryotherapy, the inflatable balloon may be introduced at atreatment site inside a patient, and the balloon may be positioned andinflated. Once the balloon is positioned, a cryogenic agent may beprovided by a source external to the patient at the proximal end of thecryotherapy catheter, and delivered distally through a lumen to thecooling chamber, where it may be released. Release of the cryogenicagent into the chamber can cool the chamber (e.g., through theJoule-Thomson effect), and correspondingly, the balloon's outer surface,which may be in contact with tissue that is to be ablated. Gas resultingfrom release of the cryogenic agent may be exhausted proximally throughan exhaust lumen to a reservoir or pump external to the patient. As aresult of the release of the cryogenic agent into the chamber and theexhausting of the resulting gas from the chamber, tissue adjacent to theballoon may be cooled to a therapeutic level (e.g., 0° C., −20° C., −40,−60° C., −80° C., or some other appropriate value) for an appropriateperiod of time.

SUMMARY

When a cryotherapy catheter is employed to deliver cryotherapy to atreatment site internal to a patient, such as to a patient's left orright atrium (e.g., to treat atrial fibrillation), it may beadvantageous to focus the cryotherapy on a precise region of tissue tobe treated. In order to focus the cryotherapy on a precise location,portions of the outer surface of an inflatable balloon portion can beinsulated from the cryogenic agent by having nested balloons. Forexample, an inner balloon can be adapted to receive the cryogenic agentand an outer balloon can be spaced from the inner balloon such that itsexternal surface is thermally insulated from a cryogenic agent internalto the inner balloon. The cryotherapy can then be delivered bymanipulating the cryotherapy catheter such that the inner ballooncontacts a portion of the outer balloon adjacent to a desired targettissue region. The remainder of the outer balloon can remain spaced fromthe inner balloon to insulate and protect non-targeted tissue that maybe in contact with the outer surface of the outer balloon during atreatment procedure. The thermally insulated regions can also protectother bodily fluids that may come into contact with the outer balloon(e.g., blood). An insulating space can be maintained between the innerballoon and the outer balloon by applying a positive pressure betweenthe two balloons.

A pressure regulator can be used to maintain the positive pressurebetween the two balloons. In some embodiments, the pressure regulator isa valve that can be closed to maintain a desired amount of fluid withinthe space between the outer balloon and the inner balloon. In otherembodiments, the pressure regulator can include one or more fluid flowcontrollers to control the flows of fluid into and/or out of the spacebetween the outer balloon and the inner balloon. Leaks in one or both ofthe balloons can be detected by monitoring the pressure within the spacebetween the two balloons with a pressure sensor. In some embodiments,the outer balloon can include a wall having compressible structures thatcan be compressed to reduce the insulative effect of the outer wall.

In a first aspect, a cryotherapy system includes a cryotherapy catheterhaving an inflatable balloon portion and a pressure regulator. Theinflatable balloon portion includes an outer balloon and an innerballoon within the outer balloon. The inner balloon is configured toreceive, during a cryotherapy procedure, a cryogenic agent forextracting heat from body tissue at a desired location. The inflatableballoon portion is at a distal end of the cryotherapy catheter. Thepressure regulator is adapted to maintain a positive pressure betweenthe inner balloon and the outer balloon during a cryotherapy procedure.

The cryotherapy system can include a detector to monitor the pressurebetween the inner balloon and the outer balloon and to determine whethera leak of the inner or outer balloon has occurred. For example, a leakof the outer balloon can be detected by a decrease of the pressurebetween the inner balloon and the outer balloon; and a leak of the innerballoon can be detected by an increase of the pressure between the innerballoon and the outer balloon.

The pressure regulator can maintain a positive pressure between theinner balloon and the outer balloon sufficient to maintain a gas spacebetween the inner balloon and the outer balloon when the outer balloonis within a body lumen. For example, the pressure regulator can maintaina positive pressure of between 0.1 and 2 psi greater than bloodpressure. In some embodiments, the pressure regulator is a valve and thepositive pressure is maintained by closing the valve once a spacebetween the outer balloon and the inner balloon is filled with apredetermined amount of fluid.

The outer balloon can be more compliant than the inner balloon. Theouter balloon can be made of a polymer. In some embodiments, the outerballoon is a thermoplastic elastomer, such as polyether block amide,which is sold under the trade name Pebax®. In other embodiments, theouter balloon can be a urethane. The inner balloon can be made ofpolyolefin copolymer, polyester, polyethylene teraphthalate,polyethylene, polyether-block-amide, polyamide, polyimide, latex, aurethane-family material, neoprene, and poly ether amide blockcopolymer.

The outer balloon, in some embodiments, includes a wall havingcompressible structures that can be compressed to reduce the insulatingproperties of the wall of the outer balloon. The compressible structurescan be selected from the group consisting of air pockets, liquidpockets, gel pockets, dimples, open cell foam, and combinations thereof.

In another aspect, a cryotherapy catheter includes an inflatable balloonportion at a distal end of the cryotherapy catheter. The inflatableballoon portion includes an outer balloon and an inner balloon withinthe outer balloon. The inner balloon is adapted to receive a cyrotherapyagent. The outer balloon has a wall including a plurality ofcompressible structures that provide an insulating property, such thatthe outer balloon can be compressed between the inner balloon and atarget tissue region to reduce the insulating property of a compressedportion of the wall of the outer balloon, to extract heat from thetarget tissue region. In some embodiments, the plurality of compressiblestructures are air pockets, dimples, open cell foam, and combinationsthereof.

In another aspect, a method of detecting a leak in a two-ballooncryotherapy catheter includes using a cyrotherapy catheter having adistal end that includes an inflatable balloon portion having an outerballoon and an inner balloon within the outer balloon. The methodincludes, introducing a distal end of the cyrotherapy catheter to adesired anatomical location, applying a positive pressure to inflate aspace between the outer balloon and the inner balloon with a fluid,detecting changes in pressure of the space between the outer balloon andthe inner balloon, and providing an alert adapted to notify a user of acondition if a change in pressure indicating a breach of the innerballoon or the outer balloon has occurred.

The method can include filling the inner balloon with a cryogenic agentwhile maintaining a positive pressure in the space between the outerballoon and the inner balloon. The method can also include manipulatingthe cryotherapy catheter such that a wall of the inner balloon makescontact with a wall of the outer balloon, to extract heat from acorresponding target issue region. The positive pressure in the spacebetween the outer balloon and the inner balloon can be maintained atbetween 0.1 and 2 psi greater than blood pressure.

The method can include a process of retracting the distal end of thecryotherapy catheter from the desired anatomical location. Theretracting step can include the steps of, deflating the inner balloonwhile maintaining the positive pressure in the space between the innerballoon and the outer balloon, releasing the positive pressure from thespace between the outer balloon and the inner balloon to fully deflatethe inflatable balloon portion, and removing the deflated inflatableballoon portion from the desired anatomical location. Another deflationprocess could include releasing the positive pressure between the innerand outer balloon, then deflating inner and outer balloonsimultaneously, and removing the deflated inflatable balloon portionfrom the desired anatomical location.

In another aspect, a method of performing cryotherapy includes using acyrotherapy catheter having a distal end that includes an inflatableballoon portion having an outer balloon and an inner balloon within theouter balloon. The method includes the steps of introducing a distal endof a cryotherapy catheter to a desired anatomical location, applying apositive pressure to inflate the space between the outer balloon and theinner balloon, filling the inner balloon with a cryogenic agent, andmanipulating the cryotherapy catheter such that a wall of the innerballoon makes contact with a wall of the outer balloon to extract heatfrom a corresponding target issue region.

The positive pressure in the space between the outer balloon and theinner balloon can be maintained at between 0.1 and 2 psi greater thanblood pressure.

The method can include a process of retracting the distal end of thecryotherapy catheter from the desired anatomical location. Theretracting step can include the steps of deflating the inner balloonwhile maintaining the positive pressure in the space between the innerballoon and the outer balloon, releasing the positive pressure from thespace between the outer balloon and the inner balloon to fully deflatethe inflatable balloon portion, and removing the deflated inflatableballoon portion from the desired anatomical location. Another deflationprocess could include releasing the positive pressure between the innerand outer balloon, then deflating inner and outer balloonsimultaneously, and removing the deflated inflatable balloon portionfrom the desired anatomical location.

The method can include filling the space between the inner balloon andthe outer balloon with a fluid selected from the group of nitrogen,oxygen, argon, carbon dioxide, nitrous oxide, helium, krypton, sugarsolutions, saline solutions, polyols, glycols, dimethyl sulfoxide, andmixtures thereof. In some embodiments, a contrast agent can be used asthe insulating fluid. The methods can include filling the inner balloonwith a cryotherapy agent selected from liquid nitrogen, nitrous oxide,carbon dioxide, methane, ethane, butane, propane, chlorofluorocarbons,hydrochlorofluorocarbons, and mixtures thereof.

The details of one or more embodiments are set forth in the accompanyingdrawings and the description below. Other features, objects, andadvantages will be apparent from the description and drawings, and fromthe claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates an example cryotherapy catheter having two nestedballoons.

FIG. 2 illustrates an example of how the cryotherapy catheter of FIG. 1can be used to deliver cryotherapy to a desired location.

FIG. 3 illustrates another example implementation of double ballooncryotheraphy catheter.

FIGS. 4A-4G illustrate example embodiments of a double balloon catheterhaving an outer balloon having a wall having compressible structures.

FIG. 5 illustrates an example implementation of a balloon catheterhaving multiple inner balloons within an outer balloon.

FIG. 6 is a flow chart with steps of using the cyrotherapy system ofclaim 1.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

When a cryotherapy catheter is employed to deliver cryotherapy to atreatment site internal to a patient, such as to a patient's left orright atrium (e.g., to treat atrial fibrillation), it may beadvantageous to focus the cryotherapy on a precise region of tissue tobe treated. An inflatable balloon portion at a distal end of acryotherapy catheter is used to deliver the cryotherapy. The inflatableballoon portion includes multiple nested balloons, including at leastone inner balloon adapted to receive a cryogenic agent. The inflatableballoon portion also includes an outer balloon that insulatesnon-targeted tissue and body fluids from the cryogenic agent(s) withinthe inner balloon. The cyrotherapy catheter can be manipulated such thatthe inner balloon contacts a portion of the outer balloon to allowbetter heat transfer between a portion of the surface of the outerballoon and the inner balloon to extract heat (and thus delivercryotherapy) to a target tissue region. For example, a portion of theouter balloon can be pressed against the target tissue region such thatthe outer balloon deforms and makes contact with the inner balloonadjacent the target tissue region.

FIG. 1 illustrates an example balloon catheter 101 having an inflatableballoon portion 102. The inflatable balloon portion 102 includes aninner balloon 104 nested within an outer balloon 106. The balloons 104and 106 are depicted as inflated. The inner balloon 104 can be employedto deliver cryotherapy to a treatment site internal to a patient. Duringuse, a positive pressure can be applied to and maintained in a space 118between the inner balloon 104 and the outer balloon 106. The positivepressure can be imparted by filling the space 118 with an insulatingfluid. The inner balloon 104, when inflated with a cryogenic agent, canbe used to deliver cryotherapy (or more precisely, to extract heat fromadjacent body tissue) by pressing the outer balloon 106 against thedesired anatomical location(s) such that the inner balloon 104 makescontact with the outer balloon 106. The surrounding regions of the outerballoon 106 where the outer balloon 106 does not contact the innerballoon 104 are thermally insulated from the cooling effect of thecryogenic agent. For example, as shown in FIG. 2, when pressed against apulmonary vein wall, the cryoablation will be limited to a contactregion 202 between the two balloons. In some embodiments, the contactregion can be in the form of an annular band around the outer surface ofthe outer balloon 106. The insulating fluid between the two balloonsacts as an insulator to protect non-target tissues.

To deliver cryotherapy, the cryotherapy balloon catheter 101 shown inFIG. 1 can be configured to deliver a cryotherapy fluid (e.g., acryogenic agent) from an external cryogenic agent source 117 to theinner balloon 104, through a cryogenic agent supply lumen 120. Insidethe inner balloon 104, the cryogenic agent can be released through acooling device 123. For example, the cooling device 123 can include acoiled portion of the supply lumen 120 having one or more orificesthrough which certain cryogenic agents can exit, some of which canundergo a liquid-to-gas phase change that cools the balloon 104 byevaporation. Gas resulting from the cryogenic agent being releasedinside chamber 119 can be exhausted through a separate exhaust lumen126. For example, gas can be exhausted through the exhaust lumen 126 toan external vacuum pump 129. During use, the inner balloon 104 can befilled with a cryogenic agent to a pressure of between 5 psig and 15psig. In some embodiments, the inner balloon 104 can be filled to apressure of about 8 psig. A positive pressure can be applied to thespace 118 between the inner balloon 104 and the outer balloon 106 byfilling the space 118 with an insulating fluid. The insulating fluid canbe introduced via an insulating fluid supply line 122 from an externalinsulating fluid source 123. The positive pressure can then bemaintained by closing a valve 124 in the insulating fluid supply line.The space between the balloons can include a pressure sensor 125. Asshown, the pressure sensor 125 is connected to an outer portion of theinsulating fluid supply line. In other embodiments, the pressure sensor125 can be positioned on an outer surface of the inner balloon 104 or onan inner surface of the outer balloon 106. In some embodiments, thepressure sensor 125 can be a pressure sensing lumen with a distal endpositioned between balloons 104 and 106. The pressure sensor can be usedto monitor the pressure in the space 118, which can assist the fillingof the space 118, to dynamically maintain a desired positive pressure,and/or to detect the presence of leaks in either of the balloons. Leakscan be detected by monitoring the pressure of the space 118. An increasein pressure can indicate a leak in the inner balloon 104 to space 118. Adrop in pressure can indicate a leak in the outer balloon 106.

The positive pressure between the outer balloon 106 and the innerballoon 104 can be maintained at a pressure of less than the pressurewithin the inner balloon 104 during a cryotherapy treatment but at apressure sufficient to maintain a space between at least a portion ofthe inner balloon 104 and the outer balloon 106. In some embodiments,the positive pressure within space 118 can be less than 4 psig. In someembodiments, the positive pressure is greater than 0.1 psi greater thanblood pressure and/or less than 2 psi greater than blood pressure. Thepositive pressure can be maintained at greater than 0.3 psi greater thanblood pressure and less than 1.5 psi greater than blood pressure. Forexample, the positive pressure can be maintained at about 0.5 psigreater than blood pressure. The positive pressure maintained betweenthe outer balloon 106 and the inner balloon 104 can impact how the outerballoon 106 conforms to anatomical structures. The lower the positivepressure, the more easily the outer balloon 106 can conform to irregularanatomical structures (e.g., an irregular PV antrum anatomy). Having theouter balloon 106 that easily conforms to anatomical structures canreduce the incidences of blood leakage past the outer balloon 106, whichthus reduce the need for other measures for preventing blood leakagepast the inflatable balloon portion of the cryotherapy catheter, such asapplying pressure to the anatomical structures with the outer balloon orprecise positioning of the outer balloon.

The elasticity of the outer balloon 106 can also impact the ability ofthe outer balloon 106 to conform to irregular anatomical structures. Insome embodiments, the outer balloon is more complaint than the innerballoon. The outer balloon can be made of an elastic material. In someembodiments, the outer balloon 106 is more elastic than the innerballoon 104. For example, the outer balloon can be a polyether blockamide, which is sold under the trade name Pebax®. In other embodiments,the outer balloon can be a urethane. The inner balloon can be formedfrom a polymer including, but not limited to, polyolefin copolymer,polyester, polyethylene teraphthalate, polyethylene,polyether-block-amide, polyamide (e.g., nylon), polyimide, latex, aurethane-family material, neoprene, etc. In particular, for example,certain embodiments of the inner balloon 104 include PEBAX® 7033material (70D poly ether amide block). In other embodiments, both theinner and outer balloon can be made of the same material, e.g., apolyether block amide. In some embodiments, the balloons 104 and/or 106can be constructed by blow-molding a polymer extrusion into the desiredshape. In other embodiments, the balloon s 104 and/or 106 can beconstructed by dipping a mandrel in an appropriate liquid material, andallowing the material to cure. In some embodiments, the inner balloon104 can be constructed to expand to a desired shape when pressurizedwithout elastically deforming substantially beyond the desired shape.

The insulating fluid can be a liquid or a gas. The particular insulatingfluid can impact the function of the balloon catheter 101. For example,the specific heat capacity, the compressability, and the viscosity ofthe insulating fluid can all impact the function of the balloon catheter101. The insulating fluid can be non-toxic. In some embodiments, theinsulating fluid can be one or more of the following gasses: nitrogen,oxygen, carbon dioxide, argon, nitrous oxide, and helium, krypton. Forexample, the insulating fluid can be atmospheric air (a mixture ofnitrogen, oxygen, argon, and carbon dioxide). In other embodiments, theinsulating fluid can be a cryoprotectant. Cryoprotectants include sugarsolutions (e.g., solutions of sucrose, trehalose, and/or glucose),saline solutions, polyols, glycols (e.g., ethylene glycol, propyleneglycol, glycerol), and dimethyl sulfoxide (DMSO). The insulating fluidcan include a contrast agent. For example, the insulating fluid caninclude iodine or barium. For example, a cryoprotectant that includesone or more radiopaque additives (e.g., iodine or barium) can be used asan insulating fluid. The use of a contrasting insulating fluid canpermit a physician to track the progress of the balloons and/or toidentify contact between the balloons during the delivery ofcyrotherapy.

A pressure regulator can be used to maintain the positive pressure. Insome embodiments, the pressure regulator can be a valve that can beclosed to maintain a desired amount of fluid within the space betweenthe outer balloon and the inner balloon. When the insulating fluid isnot recirculated during a cyrotherapy procedure, a single valve can be asufficient pressure regulator to maintain the positive pressure. Inother embodiments, the insulating fluid can be recirculated during theprocedure and the positive pressure can be maintained by using apressure regulator that includes one or more fluid flow controllers thatcontrol the flow of the insulating fluid into and out of the spacebetween the outer balloon 106 and the inner balloon 104. The pressureregulator can, in some embodiments, adjust the flow of insulating fluidbased on a detected pressure within the space between the outer balloon106 and the inner balloon 104. In some embodiments, recirculatedinsulating fluid can absorb ambient heat and body heat to maintain atemperature sufficient to insulate the body from the cryotherapy agent.In other embodiments, a heating system can be employed to reheatrecirculated insulating fluid temperature. A temperature control system,using a temperature sensor, can be used to ensure that the insulatingfluid does not fall below a predetermined temperature within the spacebetween the outer balloon and the inner balloon.

Maintaining a positive pressure in between the inner balloon 104 and theouter balloon 106 can reduce the amount of cryogenic agent needed byreducing the amount of heat absorbed from the regions adjacent to thetarget anatomical location. The diameter of the cryogenic agent supplylumen 120 can be adjusted accordingly. The inner balloon 104 can befilled to a pressure of between 5 psig and 15 psig (e.g., about 8 psig).The cryogenic agent can be liquid nitrogen, nitrous oxide, carbondioxide, methane, ethane, butane, propane, chlorofluorocarbons,hydrochlorofluorocarbons, or a mixture thereof.

Maintaining a positive pressure in between the inner balloon 104 and theouter balloon 106 during a cyrothereapy procedure (e.g., cryoablation)can also reduce complications during the retraction procedure. After acyrothereapy procedure, the inner balloon 104 can be deflated whilemaintaining the positive pressure in the space between the outer balloon106 and the inner balloon 104. The space between the balloons can thenbe deflated by opening valve 124. Deflating the balloons in this ordercan ensure that the balloons refold properly by eliminating frictionalforces between the two balloons. Frictional forces can cause balloons torefold improperly. After the balloons are deflated and refolded, thedistal end of the balloon catheter 101 can be removed from the body.Improperly folded balloons can complicate the retraction process (e.g.,by making the retraction of balloons into a sheath 140 difficult). Animproperly retracted inflatable balloon portion can cause damage to bodyvessels as the cryotherapy catheter is removed.

To facilitate coupling the catheter 101 to external equipment, such asthe source 117 of a cryogenic agent, the source 123 of an insulatingfluid, or the vacuum pump 129, the catheter 101 can include a portcomponent 132 having a number of coupling members 135A, 135B, and 135C.The coupling members 135A, 135B, and 135C can, in some embodiments,terminate lumens that are internal to the catheter shaft (e.g., thecryogenic agent supply lumen 120, the insulating fluid supply lumen 122,and the exhaust lumen 126) with connectors (e.g., industry-standardmedical connectors, proprietary medical connectors, other connectors,etc.) that facilitate connection of the lumens 120, 122, and 126 to theexternal equipment (e.g., with medical tubing). As shown in FIG. 1, theport component 132 is merely exemplary. Other connections andconfigurations are possible and contemplated (e.g., connections forpressure sensor(s), electrical sensor(s), multiple vacuum ports, etc.).

In the example of FIG. 1, the balloon catheter 101 is an over-the-wirecryotherapy balloon catheter, having a guidewire 111 disposed inside aguidewire lumen 114. In the implementation depicted, the port component132 can also provide access to the guidewire lumen 114 and correspondingguidewire 111. In other embodiments, the balloon catheter can be free ofthe guidewire 111. In some embodiments, the balloon catheter 101 canhave other means for maneuvering the balloon catheter 101 though thecirculatory system.

As shown in the example of FIG. 1, the balloon catheter 101 is disposedin a delivery sheath 140. In other embodiments, the delivery sheath 140is not included. In some embodiments that have a delivery sheath, thedelivery sheath 140 is a hollow tube that can be initially placed insidea patient and subsequently used as a conduit for other medical devices,such as the balloon catheter 101. For procedures in which severalcatheters may be employed (e.g., catheters of different sizes or havingdifferent characteristics or functions), the delivery sheath 140 canprotect the patient's internal body organs and body lumens through whichthe various medical devices are navigated. In addition, the deliverysheath 140 can facilitate easier navigation of other medical devices, bya physician or other technician, to a treatment site.

The delivery sheath 140 may be steerable, and it may be characterized bya specific diameter, length, distal feature, etc. For example, deliverysheaths may be available in varying diameters, such as 8.5 Fr (French),10 Fr, 11 Fr, etc.; varying lengths, such as 60 cm, 65 cm, 71 cm, 78 cm,90 cm, etc.; and having distal ends that are biased in various shapes,such as, for example, in a 15° curve, a 55° curve, a short 120° curve, along 120° curve, etc. Different delivery sheaths may be configured fordifferent procedures. For example, a delivery sheath having one biasedcurvature may be particularly effective for guiding an inner balloon toa patient's pulmonary veins to treat atrial fibrillation, while adelivery sheath having a different biased curvature may be particularlyeffective for another procedure, such as one in which a stent isdelivered and positioned within a patient's vasculature.

In some embodiments, as depicted in FIG. 1, a distal tip 145 of thedelivery sheath 140 is slightly tapered, for example, to facilitatenavigation of the tip 145 through a patient's vasculature, or tofacilitate crossing of tissue membranes of the patient (e.g., the septalwall, during a procedure to treat atrial fibrillation). A proximal end148 may be tapered to more easily receive other medical devices, such asthe balloon catheter 101 that is shown disposed in the delivery sheath140.

Exemplary cryotherapy catheters can include other components andstructures that are not shown in FIG. 1. In particular, for example, acryotherapy catheter may include one or more temperature sensors inchamber 119, on or in the balloon, on a shaft 110, etc. A pressuresensor, e.g., a pressure sensing lumen, can be included to detectpressure within inner balloon 104 or, as discussed above, in the spacebetween the inner and outer balloons. Various electrodes can be includedon the outer balloon 106 (e.g., to sense electrical activity in tissueto potentially be treated, or to stimulate electrical activity in suchtissue). Other features are possible and contemplated.

By having a double balloon design where a small positive pressure ismaintained between the outer balloon and the inner balloon, cyrotherapycan be limited to the tissues that pressed against the outer balloon 106with sufficient strength to make the outer balloon 106 contact the innerballoon 104 in that region. For example, when the double balloon ispressed against the pulmonary vein wall, as shown in FIG. 2, thecryoablation region can be limited to that annular contact region 202where the balloons contact each other and press against the pulmonaryvein wall. The placement of the cryoablation contact region can bedetermined by the shapes and/or positioning of the inner balloon 104 andthe outer balloon 106. For example, as shown in FIG. 3, the innerballoon can be positioned towards a distal end of the outer balloon suchthat the balloons preferentially contact each other at a distal end ofthe inflatable balloon portion. Arrangement and shapes of the twoballoons can be adapted for particular applications of cryotherapy. Inother embodiments, certain portions of the outer and inner balloons canbe positioned to always be in contact. For example, certain portions ofthe inner and outer balloons can be adhered.

An outer balloon 106 can also be designed to include compressiblestructures. For example, outer balloons 106 having compressiblestructures are depicted in FIGS. 4A-4G. As shown in FIG. 4A, a series ofcompressible structures 202 can be uniformly arranged about the wall ofthe outer balloon 106. The compressible structures 202 can separater theinner balloon from an outer surface of the outer balloon and thusinsulate body tissues and fluids from any cryotherapy agent within theinner balloon. When the cryotherapy catheter is manipulated to press theouter balloon against a target tissue region, however, the compressiblestructures in the region of the outer balloon wall adjacent the targettissue region can be compressed between the target tissue region and theinner balloon and thus allow for a better transfer of heat from thetarget tissue region to the inner balloon. Accordingly, cryotherapy canbe applied to a target tissue region while insulating surroundingnon-target tissues.

FIG. 4B depicts an implementation of the outer balloon 106 having aninner wall 209 and an outer wall 208 that define a fixed fluid filledpockets 206 therebetween. The pockets 206 can be filled with aninsulating fluid, e.g., a gas or liquid such as those discussed above.In other embodiments, the pockets 206 can be filled with a gel. Theinner wall 209 and the outer wall 208 are connected by ribs 204 thathold the walls together. The ribs 204 allow for fluid to pass from eachpocket 206 to adjacent pockets 206. Accordingly, as shown in FIG. 4C,when the outer balloon 106 is pressed against a target tissue region,such an adjacent region of the outer balloon 106 is compressed betweenthe target tissue region and the inner balloon 104, fluid in the pockets206 in the compressed portion of the outer balloon 106 flows throughribs 204 to adjacent pockets and thus allows for better heat transferbetween the target tissue region and the inner balloon. As shown in FIG.4E, the outer balloon 106 can also include smaller compressible pockets222. The compressible pockets 222 can also be filled with an insulatingfluid. In other embodiments, as shown in FIG. 4G, the outer balloon caninclude an open cell foam that can be compressed under pressure toreduce its insulating effects.

FIG. 4D depicts an implementation of an outer balloon 106 havingpreformed dimples 212. The preformed dimples 212 can be uniformlypositioned about the outer balloon. The dimples 212 preferentiallycontact the inner balloon such that the majority of outer balloon isspaced from the inner balloon by fluid space 216. The fluid spaceinsulates the majority of the outer balloon from the inner balloon.Accordingly, when the outer balloon 106 is pressed against a targettissue region, such an adjacent region of the outer balloon 106 iscompressed between the target tissue region and the inner balloon 104,the preformed dimpled deform to allow the portion of the outer balloon106 adjacent the target tissue region to contact the inner balloon 104and thus allow for better heat transfer between the target tissue regionand the inner balloon.

FIG. 4F depicts an implementation of an outer balloon 106 havinginternally formed collapsible bumps 232. The bumps 232 can define aninternal space 236. Internal spaces 236 can include a fluid. Forexample, the internal spaces 236 can be filled with a gas or liquid suchas those discussed above. In other embodiments, the internal spaces 236can be filled with a gel. In some embodiments, the outer surface of theouter balloon is smooth. The collapsible bumps can position the innerballoon away from the outer balloon. The collapsible bumps are adaptedto collapse when the outer balloon is compressed between a target tissueregion and the inner balloon 104.

FIG. 5 depicts an implementation of an inflatable balloon portion havingtwo inner balloons 104A and 104B nested within outer balloon 106. Thetwo inner balloons can be alternatively inflated with a cryogenic agentand/or an insulating fluid to control the portions of the outer balloon106 that contact portions of an inner balloon that includes a cryogenicagent. In other embodiments, the inflatable balloon portion 102 caninclude additional inner balloons and/or can include a subdivided innerballoon.

FIG. 6 is a flowchart of a process of using the cyrotherapy system ofFIG. 1. The process 600, includes a first step of delivering a distalend of the cryotherapy catheter to a desired anatomical location 610.The desired anatomical location can be adjacent to a target tissueregion for cyrotherapy. A distal end includes an inflatable balloonportion including an outer balloon 106 and an inner balloon 104 nestedwithin the outer balloon. During the delivery process, the inner andouter balloons are deflated. The delivery process can include passingthe distal end of the cryotherapy catheter though a sheath. In someembodiments, the cryotherapy catheter is delivered into or adjacent tothe heart.

Once the distal end of the cryotherapy cather is delivered to a desiredanatomical location, the process 600 includes a step of inflating theinflatable balloon portion 102. The space between the inner balloon andthe outer balloon is inflated with an insulating fluid in step 620 toprovide an insulating layer between the inner balloon and surroundingtissues and body fluids. The inner balloon is inflated in step 630. Apressure between the inner balloon 104 and the outer balloon 106 can bemonitored via a presser sensor to detect pressure changes indicating aleak in either the inner and/or outer balloon. The pressure can bemonitored throughout the procedure.

Once the inner and outer balloons are inflated, the inflatable balloonportion 102 is pressed against the target tissue region in step 640 inorder to have the outer balloon 106 deform to contact a portion of theinner balloon 104 adjacent to the target tissue region. For example, asshown in FIG. 2, when pressed against a pulmonary vein wall, thecryoablation can be limited to a contact region 202 between the twoballoons, as shown in FIG. 2. The inner balloon 104 then receives acryogenic agent in step 650 to provide a means to extract heat form atarget tissue region. In some embodiments, the treatment pattern shapecorresponds to at least a portion of a Maze pattern. The inflatableballoon portion 102 can be configured to be inflated inside a patient'sleft atrium in a manner in which the external surface of the outerballoon 106 contacts multiple pulmonary vein ostia (e.g., the leftsuperior pulmonary vein and left inferior pulmonary vein). The treatmentpattern shape can be configured to ablate tissue around multiplecorresponding ostia (e.g., in a pattern corresponding to at least aportion of the ablation patterns). For example, the cryotherapy cathetercan be routed to the patient's left atrium through the patient's femoralvein, into the inferior vena cava and right atrium, through the septalwall, and into the left atrium. Cyrotherapy catheters can also beemployed in various other procedures and/or be routed to a desiredanatomical location via other paths.

Once the cryotherapy is completed, the inflatable balloon portion 102 isdeflated to allow for the cryotherapy catheter to be removed from theanatomical location. The inner balloon 104 is deflated in step 660 tohave the inner balloon retract without interference from the outerballoon 106. The space 119 between the inner balloon 104 and the outerballoon 106 is deflated in step 670 to fully deflate the inflatableballoon portion 102. By deflating the inner balloon first whilemaintaining the positive pressure in the space between the inner andouter balloons reduces that chances that the inner and outer balloonswill interact causing the balloons to fold in improper ways that wouldcomplicate the extraction of the inflatable balloon portion 102. Oncethe inflatable balloon portion 102 is fully deflated, the distal end ofthe cryotherapy catheter is removed from the body in step 680.

The use of the outer balloon 106 insulates non-target tissues andsurrounding body tissues from the cryogenic agents within the innerballoon 104. Accordingly, less heat is absorbed by the cryogenic agentswithin the inner balloon 104, thus reducing the amount of cryogenicagent needed to successfully complete the cyrotherapy of the targettissue region. Furthermore, the outer balloon 106 occupies a largerspace internally than the inner balloon and can be complaint with bodytissues. Accordingly, the outer balloon 106 can conform to thesurrounding body tissues, including non-target tissue regions. Forexample, the outer balloon can also be used to reduce the flow of bloodto the target tissue region. The outer balloon can, in some embodiments,be a compliant balloon and be inflated to variable diameters/shapes(depending on pressure) in order to obtain occlusion regardless of avariety of anatomical geometries, including non-symmetrical anatomicalgeometries.

A number of ancillary processes may be used to affect the materialproperties of the balloons 104 and/or 106. For example, the polymerextrusion may be exposed to gamma radiation which can alter the polymerinfrastructure to provide uniform expansion during blow molding andadditional burst strength when in use. In addition, the formed balloons104 and/or 106 may be exposed to a low temperature plasma field whichcan alter the surface properties to provide enhanced adhesioncharacteristics. Other materials and manufacturing processes can be usedto provide the balloons 104 and/or 106 with desired characteristics.

A number of embodiments have been described. Nevertheless, it will beunderstood that various modifications may be made without departing fromthe spirit and scope of this document. In particular, for example,cryotherapy balloon catheters are described as employing theJoule-Thomson effect to cool using a liquid-to-gas phase change, butliquid-based cryocatheters can also include cooling regions andthermally insulated regions. Moreover, cryotherapy catheters can beemployed to deliver targeted cryotherapy to regions of a patient's bodyother than the patient's heart (including, for example, a patient'sprostate gland, or other glands; a portion of the patient'sgastro-intestinal tract; a small (e.g., varicose) vein; or othersuitable internal treatment sites). Multiple cooling and thermallyinsulating regions can be provided, and the regions can be formed invarious shapes and sizes. Accordingly, other embodiments are within thescope of the following claims.

1. A cryotherapy system comprising: a cryotherapy catheter comprising aninflatable balloon portion at a distal end of the cryotherapy catheter,the inflatable balloon portion having an outer balloon and an innerballoon within the outer balloon; the inner balloon configured toreceive during a cryotherapy procedure a cryogenic agent for extractingheat from body tissue at a desired location; and a pressure regulator tomaintain a positive pressure between the inner balloon and the outerballoon during a cryotherapy procedure.
 2. The cryotherapy system claim1, further comprising a detector to monitor the pressure between theinner balloon and the outer balloon and to determine whether a leak ofthe inner or outer balloon has occurred.
 3. The cryotherapy system ofclaim 1, wherein the pressure regulator maintains a positive pressurebetween the inner balloon and the outer balloon sufficient to maintain afluid space between the inner balloon and the outer balloon when theouter balloon is within a body lumen.
 4. The cryotherapy system of claim1, wherein the pressure regulator maintains a positive pressure ofbetween 0.1 and 2 psi greater than blood pressure.
 5. The cryotheraphysystem of claim 1, wherein the pressure regulator comprises a valve andmaintains the positive pressure by closing the valve once a spacebetween the outer balloon and the inner balloon is filled with apredetermined amount of fluid.
 6. The cryotherapy system of claim 1,wherein the outer balloon is more compliant than the inner balloon. 7.The cryotherapy system of claim 1, wherein the outer balloon comprises amaterial selected from the group consisting of urethane, polyether blockamide, and combinations thereof.
 8. The cryotherapy system of claim 1,wherein the outer balloon comprises a wall comprising a plurality ofcompressible structures, wherein the compression of the compressiblestructures reduces an insulating property of the wall of the outerballoon.
 9. A cryotherapy catheter comprising an inflatable balloonportion at a distal end of the cryotherapy catheter, the inflatableballoon portion comprising: an inner balloon adapted to receive acryoptherapy agent; and an outer balloon having a wall comprising aplurality of compressible structures that provide an insulatingproperty, the inner balloon being within the outer balloon such that thesurface structures are adapted to be compressed between a target tissueregion and the inner balloon to reduce the insulating property of acompressed portion of the wall of the outer balloon to extract heat fromthe target tissue region.
 10. The cryotherapy catheter of claim 9,wherein the plurality of compressible structures are selected from thegroup consisting of air pockets, liquid pockets, gel pockets, dimples,open cell foam, and combinations thereof.
 11. A method of detecting aleak of a two-balloon cryotherapy catheter, the method comprising:introducing a distal end of the cryotherapy catheter to a desiredanatomical location, the distal end comprising an inflatable balloonportion, the inflatable balloon portion having an outer balloon and aninner balloon within the outer balloon; applying a positive pressure toinflate a space between the outer balloon and the inner balloon with afluid; detecting changes in pressure of the space between the outerballoon and the inner balloon; and providing an alert adapted to notifya user of a condition if a change in pressure indicates that a breach ofthe inner balloon or the outer balloon has occurred.
 12. The method ofclaim 11 further comprising filling the inner balloon with a cryogenicagent while maintaining a positive pressure greater than blood pressurein the space between the outer balloon and the inner balloon.
 13. Themethod of claim 11 further comprising manipulating the cryotherapycatheter such that a wall of the inner balloon makes contact with a wallof the outer balloon to extract heat from a corresponding target issueregion.
 14. The method of claim 11, wherein the positive pressure in thespace between the outer balloon and the inner balloon is maintained atbetween 0.1 and 2 psi greater than blood pressure.
 15. The method ofclaim 11, further comprising retracting the distal end of thecryotherapy catheter from the desired anatomical location, retractingcomprising: deflating the inner balloon while maintaining the positivepressure in the space between the inner balloon and the outer balloon;releasing the positive pressure from the space between the outer balloonand the inner balloon to fully deflate the inflatable balloon portion;and removing the deflated inflatable balloon portion from the desiredanatomical location.
 16. A method of performing cryotherapy, the methodcomprising: introducing a distal end of a cryotherapy catheter to adesired anatomical location, the distal end comprising an inflatableballoon portion, the inflatable balloon portion having an outer balloonand an inner balloon within the outer balloon; applying a positivepressure to inflate the space between the outer balloon and the innerballoon with a fluid; filling the inner balloon with a cryogenic agent;and manipulating the cryotherapy catheter such that a wall of the innerballoon makes contact with a wall of the outer balloon and the tissue tobe ablated.
 17. The method of claim 16, wherein the positive pressure inthe space between the outer balloon and the inner balloon is maintainedat between 0.1 and 2 psi greater than blood pressure.
 18. The method ofclaim 16, further comprising retracting the distal end of thecryotherapy catheter from the desired anatomical location, retractingcomprising: deflating the inner balloon while maintaining the positivepressure in the space between the inner balloon and the outer balloon;releasing the positive pressure from the space between the outer balloonand the inner balloon to fully deflate the inflatable balloon portion;and removing the deflated inflatable balloon portion from the desiredanatomical location.
 19. The method of claim 16, wherein the spacebetween the inner balloon and the outer balloon is inflated with a fluidselected from the group consisting of nitrogen, oxygen, argon, carbondioxide, nitrous oxide, helium, krypton, sugar solutions, salinesolutions, polyols, glycols, dimethyl sulfoxide, and mixtures thereof.20. The method of claim 1, wherein the cryotherapy agent is select fromnitrogen, nitrous oxide, carbon dioxide, methane, ethane, butane,propane, chlorofluorocarbons, hydrochlorofluorocarbons, and mixturesthereof.